Association Between Visceral Adipose Tissue and Chronic Respiratory Diseases: A Two-Sample Multivariable Mendelian Randomization Study in European Population

内脏脂肪组织与慢性呼吸系统疾病的关联:一项基于欧洲人群的双样本多变量孟德尔随机化研究

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Abstract

BACKGROUND: The relationship between obesity and some respiratory diseases has been well documented. However there have been few studies on the association between visceral adipose tissue (VAT) and chronic respiratory diseases (CRDs), it remains unclear whether VAT is causally associated with CRDs. METHODS: We used two-sample Mendelian randomization (MR) to illuminate the effects of VAT on four CRDs: chronic obstructive pulmonary disease (COPD), allergic asthma, interstitial lung disease (ILD), and sarcoidosis. Inverse variance weighted (IVW) served as the primary assessment method. MR Egger, weighted median, Simple mode and Weighted mode were the supplementary methods for MR analysis. We used multivariate MR analysis to adjust for the effect of body mass index (BMI) on outcomes, Egger intercept, MR-pleiotropy residual sum and outlier, and leave-one-out analysis to confirm the MR results' consistency. RESULTS: Genetically-predicted VAT was associated with an increased risk of COPD (OR = 1.56; 95% CI: 1.34-1.82; P = 1.16×10(-8)), allergic asthma (OR = 1.44; 95% CI: 1.20-1.73; P = 8.63×10(-5)), and ILD (OR = 1.15; 95% CI: 1.04-1.26; P = 4.62×10(-3)). However, there was limited evidence to support an association between VAT and sarcoidosis. In multivariate MR analysis, VAT's associations with COPD, allergic asthma, and ILD persisted after adjusting for BMI. CONCLUSION: This study provides evidence for a potential causal relationship between VAT and COPD, allergic asthma, and ILD; these relationships were independent of the effect of BMI.

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